Pharmacodynamics
Amitriptyline has antidepressant, analgesic, antianxiety, and sedative effects. The reduction of depressive symptoms is explained by the fact that a deficiency of neurotransmitters in the brain leads to depressive effects, and amitriptyline counteracts this mechanism. In the central nervous system, the drug inhibits the reuptake of neurotransmitters (primarily serotonin and norepinephrine) into the presynaptic cell, i.e., before the synapse, which increases the concentration of mood-regulating neurotransmitters between neurons. In addition, the sensitivity of the receptors is downregulated by the increased accumulation of neurotransmitters. Since this effect has a duration of about 2-3 weeks, the mood-enhancing effects are delayed.
The depressant and sleep-inducing effects of amitriptyline are due to inhibition of the neurotransmitter acetylcholine, and the analgesic effects occur due to increased serotonin concentrations.
Pharmacokinetics
The drug is rapidly absorbed after oral administration, with a bioavailability of only 30-60%. In the blood, the maximum concentration is reached 2-12 hours after oral or intramuscular administration and circulates there as well as in the tissues bound to 95% protein. Due to its fat-soluble properties, amitriptyline is distributed throughout the organism. Due to the cleavage of the methyl group and the introduction of hydroxyl groups (hydroxylation) into the molecule, amitriptyline is metabolized in the liver. As a result of genetically determined differences in hydroxylation function, 3-5% of the population have elevated plasma concentrations. The half-life is approximately 25 hours, although this is prolonged in the elderly. The drug and its intermediates are excreted mainly in the urine.
Contraindications
Amitriptyline should not be taken in case of hypersensitivity, poisoning, urinary retention or narrowing in the gastric outlet or intestinal obstruction due to intestinal paralysis.
Unless urgently needed, pregnant women should not take the antidepressant and breastfeeding women should either stop taking it or stop breastfeeding.
Drug Interactions
There should be an interval of at least 14 days between the use of tricyclic antidepressants and MAO inhibitors (e.g., tranylcypromine, selegilline, rasagilline, moclobemide) to avoid possible interactions.
Amitriptyline may reduce the effect of drugs for the treatment of high blood pressure (guanethidine, clonidine). Furthermore, amitriptyline possibly influences the effect of coumarins (e.g., phenprocoumon), which is why blood parameters should be monitored regularly during concomitant use.
An increase in effect occurs with drugs such as fluoxetine, fluvoxamine, cimetidine and neuroleptics, a decrease in effect under the simultaneous use of St. John's wort.
